High-resolution analysis of the human T-cell leukemia virus capsid protein reveals insights into immature particle morphology

Year: 2025

Type: article

Abstract: Infection with human T-cell leukemia virus type 1 (HTLV-1) can result in adult T-cell leukemia/lymphoma and HTLV-1 associated-myelopathy/tropical spastic paraparesis. The Gag polyprotein – the major structural protein – is crucial for driving virus particle assembly, with the capsid (CA) domain as the key determinant for Gag multimerization. Here, we characterize the immature CA lattice from immature virus particles by using cryo-electron microscopy and tomography (cryo-EM/ET). We report resolving the immature CA lattice to 3.4 Å resolution by single particle analysis (SPA). Our reconstruction reveals that the lattice is stabilized through a trimeric NTD inter-hexamer interface and a dimeric CTD inter-hexamer interface. Further analysis by cryo-ET reveals clear heterogeneity, notably the varying lattice curvatures and the varying distances from the CA layer to the membrane. Intriguingly, inositol hexakisphosphate (IP6) is dispensable for HTLV-1 immature particle assembly and proper immature lattice formation. These observations provide deeper insights into the molecular basis of HTLV-1 immature particle morphology as well as aid in revealing therapeutic targets. The HTLV-1 capsid (CA) domain of Gag was resolved to 3.4 Å resolution and reveals insights into immature lattice stabilization, the varying lattice curvatures and distances from the membrane, and the dispensable nature of inositol hexakisphosphate (IP6) for immature particle assembly.

Source: Nature Communications

DOI: 10.1038/s41467-025-67129-1

Authors: William G. Arndt, Alireza Ramezani, Nathaniel Talledge, Guichuan Yu, Huixin Yang, Bo Chen, Juan R. Perilla, Wei Zhang, Louis M. Mansky

Institutions: University of Minnesota, Masonic Cancer Center, University of Delaware, Minnesota Supercomputing Institute, University of Central Florida

Language: English

Topic: T-cell and Retrovirus Studies

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,990

Funders: U.S. Department of Health and Human Services, American Cancer Society, National Institutes of Health, National Institute on Drug Abuse, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Dental and Craniofacial Research

OpenAlex ID: W4417240629